Download Epigenetics Handout

Epigenetics
The information below comes from https://www.boundless.com/biology/gene-regulation/gene-expressioncan-be-controlled-through-chromatin-structure/introduction-to-epigenetics/
(For a better understanding of the enormous implications of epigenetics to your own personal health and the
health of your future children you are encouraged further to view the three very different videos found at
http://sciblogs.co.nz/code-for-life/2013/02/06/epigenetics-introductory-explanations/.)
Epigenetics is the study of changes in gene expression caused by mechanisms other than
changes in the underlying DNA sequence; hence the name "epi-genetics" (from the Greek word for
"over" or "above"). Examples of such changes might be DNA methylation or histone deacetylation,
both of which serve to suppress gene expression without altering the sequence of the silenced genes.
These changes may remain through cell divisions for the remainder of the cell's life and may also last
for multiple generations. However, there is no change in the underlying DNA sequence of the
organism; instead, non-genetic factors cause the organism's genes to be expressed differently.
Epigenetic changes, therefore, are reversible, unlike mutations of DNA.
The molecular basis of epigenetics is complex. It involves modifications of the expression of
certain genes but not the basic structure of the DNA. Additionally, the chromatin proteins associated
with the DNA may be altered. This accounts for why differentiated cells in a multicellular organism
express only the genes that are necessary for their own function. Epigenetic changes are preserved
when cells divide. Most epigenetic changes only occur within the course of one individual organism's
lifetime, but if a mutation in the DNA occurs in the sperm or egg cell that results in fertilization, then
some epigenetic changes are inherited from one generation to the next. This raises the question of
whether or not epigenetic changes in an organism can alter the basic structure of its DNA.
DNA methylation is an important regulator of gene transcription. Genes with high levels of 5methylcytosine in their promoter region are usually transcriptionally silent. DNA methylation is
essential during embryonic development; in somatic cells, patterns of DNA methylation are generally
transmitted to daughter cells with high fidelity. A large body of evidence has demonstrated that
aberrant DNA methylation is associated with unscheduled gene silencing. Aberrant DNA methylation
patterns have been associated with a large number of human malignancies and found in two distinct
forms, hypermethylation and hypomethylation, compared to normal tissue. Hypermethylation is one
of the major epigenetic modifications that repress transcription via the promoter region of tumour
suppressor genes. Hypermethylation typically occurs at CpG islands in the promoter region and is
associated with gene inactivation. Global hypomethylation has also been implicated in the
development and progression of cancer through different mechanisms.
Chromatin structure and packaging of the genome are important for regulating cellular
homeostasis. ROS-induced oxidative stress is involved in the multistage process of prostate cancer
progression. In particular, there is a growing interest in the involvement of oxidative stress in the
epigenetic regulation of gene expression and, specifically, in controlling DNA methylation. Agents
that prevent the production and chronic accumulation of ROS may play an important role in the
treatment of prostate cancer. Epigenetic alterations are clearly involved in prostate cancer initiation
and progression. Hypermethylated genes can be used to detect early stages of prostate cancer. In
addition to the use of epigenetic alterations as a means of screening, epigenetic alteration may help
clinicians predict the risk of recurrence and drug resistance. A combinatorial approach of epigenetic
therapy with antioxidant agents, along with standard radiotherapy and targeted anticancer therapy,
may help in sensitization of tumors that are resistant to current approaches of treatment. Finally, a
link between the biomarkers and therapy may have positive impact on health care.
Epigenetic modifications, such as DNA methylation, play an important role in the regulation of
gene expression, primarily through their role in regulating chromatin structure and function. Defects
in epigenetic factors are linked to several diseases. For example, Rett syndrome, a
neurodevelopmental disorder, is caused by mutations in the gene encoding methyl-CpG-binding
protein-2 (MECP2), and alpha-thalassemia/mental retardation X-linked (ATRX) syndrome is caused
by mutations in ATRX, which encodes a member of the SWI/SNF family of chromatin remodeling
proteins. Patients with ATRX syndrome exhibit severe mental retardation as well as alphathalassemia.
Epidemiological studies have established that genetic factors play a major role in the
development of schizophrenia. However, the discordance rate for schizophrenia between monozygotic
twins is approximately 50%, suggesting that epigenetic and/or environmental factors are also
involved in the development of the disease. Despite extensive research, the molecular etiology of
schizophrenia remains enigmatic. The methylation state of the genome undergoes highly dynamic
changes, extensive demethylation and reconstruction, during early embryogenesis; yet, once
established, it is very stable. Nevertheless, some epigenetic signals, including DNA methylation, can
be transmitted from one generation to the next, and are influenced by environmental or intrinsic
biological factors. Thus, DNA methylation and/or other epigenetic modifications of the genome may
help explain the ambiguity of inherited schizophrenia and the role, if any, of environmental factors in
the etiology of the disease.
You are encouraged to also see
http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/epigenetics_ethics/Introduction for an
additional article about what epigenetics is and its implications for all of us. Furthermore, you are encouraged
to be aware of future articles about the development of this field of study.